This interdisciplinary platform development partnership is led by Roswell Park Cancer Institute, with the collaboration of the Institute for Lasers, Photonics and Biophotonics at the University of Buffalo, and the Department of Chemistry at the University of Michigan. The overall goal is to develop targeted nanoparticle (NP) platforms utilizing photodynamic therapy (PDT) and multiple imaging modalities in vivo imaging and multifunctional therapeutics. We envision development, characterization and preclinical validation of multifunctional NP platforms that deliver tumor-avid, therapeutic photosensitizers (PS) that only are active (and toxic) when illuminated by light. The NP also carries a payload of one or more imaging agents, enabling both multimodal diagnosis and image-guided therapy. Selective NP delivery comes from the tumor avidity of the PS and/or from NP surface ligands that recognize targeted cells. Additional therapeutic selectivity is due to local activation of the PS by light. We hypothesize that biocompatible organically modified silicate sol (Ormosil) and polyacrylamide NP will be effective multi-functional nanovectors for tumor therapy and imaging (optical, PET, MR). Our aims are: 1. To prepare multifunctional Ormosil and polymeric nanovectors capable of both tumor therapy and imaging, which contain tumor-avid PS with or without additional targeting moieties, as well as optical, PET, and/or MRI imaging agents. 2. To characterize the different nanovectors in solution and in vitro and iteratively utilize the data within Aim 1 to select and optimize formulations. 3. To examine selected nanovectors in animal tumor systems and iteratively apply the information to Aims 1 and 2 to further refine the platform development. Allan R. Oseroff, MD, PhD, the PI, will provide overall direction and coordination and will be responsible for the cellular and animal model evaluations. Ravi Pandey, PhD (RPCI), will prepare the photosensitizers and the imaging payloads. Paras Prasad, PhD (UB), will lead development and photophysical characterization of the Ormosil platform. Raoul Kopelman, PhD (UM), will lead development and photophysical characterization the polyacrylamide platform.